US3856777A - Method of producing pyrimidine nucleoside derivatives - Google Patents

Method of producing pyrimidine nucleoside derivatives Download PDF

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US3856777A
US3856777A US00313936A US31393672A US3856777A US 3856777 A US3856777 A US 3856777A US 00313936 A US00313936 A US 00313936A US 31393672 A US31393672 A US 31393672A US 3856777 A US3856777 A US 3856777A
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derivatives
formula
compounds
anhydro
carbonate
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Y Ishido
T Yoshino
A Yamasaki
M Okutsu
H Komura
K Suzuki
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Ajinomoto Co Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06—Pyrimidine radicals

Definitions

  • R is hydroxy, mercapto, amino, acetylamino, or monolower-alkylamino
  • R is hydrogen, hydroxy, halogen, or lower alkyl
  • R is hydrogen, lower alkanoyl, or H PO in the form of the free bases, free acids, or salts of said bases and acids, are converted by reaction with cyclic lower-alkylene and lower alkenylene esters of carbonic acid at temperatures between about 100 and.200C in good yields to compounds of the formula wherein R and R are as defined above, and R is oxygen, sulfur, imino, acetylimino, or lower-alkylimino.
  • the compounds of the Formula II may be hydrolyzed in a conventional manner to arabinofuranosylpyrimidine derivatives of the formula (III) 5 5 2.
  • best yieldin terms of the pyrimidine derivative, and the term approximately equivalent, as applied to the reactants, will be understood to embrace such small excess amounts.
  • the reaction takes place fastest and with the best yields attemperatures between approximately and 200C, and may be performed conveniently in the presence of an inert solvent boiling in the preferred range so that thereaction temperature can be controlled by refluxing the mixture.
  • Dimethylformamide and diacetylformamide are suitable solvents.
  • the reaction is promoted by acetic anhydride or sodium carbonate as catalysts.
  • the compounds of Formula (II) are insoluble in many orgainc solvents, and can be precipitated from the reaction mixture by the additionof such organic solvents. They may be further purified by recrystalli zation and/or treatment with ion exchange resins or active carbon.
  • the mixture resulting from the initial dehydration reaction may be diluted with water and made acid or alkaline to promote: the hydrolysis which leads to the arabinofuranosylpyritmidine derivatives either at room temperature (15 to 25C) or at moderately elevated temperature.
  • Example l A mixture of 5 g uridine and 2.5 g ethylene carbonate was heated at C for 2 hours in an oil bath. The re action mixture was cooled to room temperature and 10 ml ethanol was added. The precipitated solid was recrystallized from 15 ml methanol containing 25 percent water and then consisted of 3.3 g pure 2,2-
  • Example 3 A mixture of 0.42 g 5 -uridylic acid triethylamine salt and 0.6 g ethylene carbonate was heated at 150C for 90 minutes in an oil bath. The reaction mixture was passed through a column of Dowex 1 X4 (formic acid type), and the effluent was evaporated in a vacuum to obtain 0.45 g 2,2'-anhydrouridylic acid.
  • Formula (I) may be employed in the reaction in the free form and as the salts of suitable acids, and the phosphoric acid esters may be employed in the form of their salts with alkali metals and amines, the triethylamine, tributylamine, and morpholine salts, for example, having convenient properties.
  • lower alkyl and analogous terms, such as lower alkanoyl, as employed in this specification and the appended claims, will be understood to cover compounds having a carbon chain of not more than four atoms.
  • the dehydrating agents employed in converting the compounds of Formula (1) into compounds of Formula ([1) thus include, but are not limited to, the cyclic ester of ethylene glycol with carbonic acid, hereinafter referred to as ethylene carbonate, and the corresponding propylene carbonate and vinylene carbonate.
  • the amount of pyrimidine derivative of Formula (1) which is converted to the corresponding compound of Formula (II) is slightly less than the stoichiometric equivalent of the alkylene or alkylenyl carbonate so that it is preferred to employ a small excess of the carbonate for Example 4
  • a mixture of 2.8 g cytidine hydrochloride and 4.4 g ethylene carbonate was heated at 150C for 50 minutes in an oil bath.
  • the reaction mixture was dissolved in ml water, and the solution was passed through a column packed with active charcoal. Then water was passed through the column to elute 2,2- anhydrocytidine hydrochloride. About 2 liters of the eluate were evaporated to dryness in a vacuum at 40 to 50C. The residue was recrystallized from a 1:1 mixture of water and ethanol.
  • the columnar crystals ob tained consisted of pure 2,2'-anhydrocytidine hydrochloride and weighed 1.33 g (51 percent yield). The compound was identified by elementary analysis and had the physical properties listed below.
  • Example 6 2.26 g 2,2'-Anhydrouridine was dissolved in ml aqueous l N sodium hydroxide, and the solution was stirred for 2 hours at room temperature. When the absorption maximum in the ultraviolet spectrum ofa sample reached 261 u, the reaction mixture was neutralized by adding Amberlite lR-120 (H type). The ionexchange resin was filtered off, and the filtrate was evaporated to 1.7 g solid l-B-D-arabinofuranosyluracil (70.5 percent yield). The ultraviolet absorption spectrum and the melting point of the crystalline material were identical with corresponding properties of a known sample.
  • Example 7 2.62 g 2,2-Anhydrocytidine hydrochloride were dissolved in 80 ml aqueous 0.1 N sodium hydroxide, and the solution was allowed to stand at room temperature for 2 hours. When the absorption maximum in the ultraviolet spectrum had reached 272 u, the reaction mixture was adjusted to about pH 2 by adding I N hydrochloric acid and evaporated to dryness in a vacuum.
  • Example 8 0.285 g N -Acetylcytidine and 0.44 g ethylene carbonate were heated in a 10 ml flask for 2 hours in an oil bath maintained at 140C. The reaction mixture was worked up as in Example 4 to obtain 0.13 g 2,2- anhydrocytadine acetate in the form of columnar crystals.
  • Example 5 4.24 g 5'-Cytidylic acid triethylamine salt and 4.4 g ethylene carbonate were dissolved in 10 ml dimethylacetamide, and the solution was refluxed for 30 minutes. The reaction mixture was passed through a first column containing 200 ml Dowex l X 4 (formic acid type), and the column was washed with water. The combined effluent and washing water were passed through a second column packed with 50 ml active charcoal and eluted with water. The eluate was evaporated in a vacuum to obtain 0.4 g 2,2'-anhydrocytidine formic acid salt.
  • Example 9 0.147 g N-Methylcytidine hydrochloride and 0.13 g ethylene carbonate were heated in a small flask for 30 minutes at 150C in an oil bath. Ethanol was added to the reaction mixture, and the solution was evaporated to obtain 0.11 g crystalline 2,2-anhydro-N methylcytidine hydrochloride percent yield). The UV spectrum of the compound showed values of max"''' 6 at 243 and 267 1..
  • R being hydrogen, alkanoyl, or H PO and R being oxygen, sulfur, imino, acetylimino, or alkylimino, said alkyl, alkanoyl, alkylene, and alkylenyl having not more than four carbon atoms.

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Abstract

Uridine, cytidine, and derivatives thereof arrived at by substitution in positions 4, 5 and 5'' are converted to the corresponding 2,2''-anhydro compounds by reaction with cyclic lower alkylene and alkenylene esters of carbonic acid. The anhydro compounds are hydrolyzed to arabinofuranosylpyrimidine derivatives in a basically known manner. The latter as well as the anhydro compounds are known physiologically active agents and/or intermediates in the synthesis of such agents.

Description

United States Patent [191 Ishido et al.
METHOD OF PRODUCING PYRIMIDINE NUCLEOSIDE DERIVATIVES Appl. No.: 313,936
Foreign Application Priority Data Dec. 14, 1971 Japan 46-101289 US. Cl 260/2115 R Int. Cl C07d 51/52 Field of Search 260/2115 R Dec. 24, 1974 [56] References Cited UNlTED STATES PATENTS 3,463,850 8/1969 Shen et a1. 260/2115 R 3,705,147 12/1972 Robins et a]. 260/2115 R Primary Examiner-Johnnie R. Brown Attorney, Agent, or Firm-Hans Berman; Kurt Kelman [57] ABSTRACT Uridine, cytidine, and derivatives thereof arrived at by substitution in positions 4, 5 and 5' are converted to the corresponding 2,2-anhydro compounds by reaction with cyclic lower alkylene and alkenylene esters of carbonic acid The anhydro compounds are hydrolyzed to arabinofuranosylpyrimidine derivatives in a basically known manner. The latter as well as the anhydro compounds are known physiologically active agents and/or intermediates in the synthesis of such agents. 1
4 Claims, No Drawings METHOD OF PRODUCING PYRIMIDINE NUCLEOSIDE DERIVATIVES This invention relates to 2,2-anhydro-uridines and the corresponding cytidine derivatives, and particularly to a method of producing such pyrimidine derivatives and to their further conversion to arabinofuranosylpyrimidine derivatives.
It has been found that pyrimidine derivatives of the formula A R. a.)
wherein R is hydroxy, mercapto, amino, acetylamino, or monolower-alkylamino, R is hydrogen, hydroxy, halogen, or lower alkyl, and R is hydrogen, lower alkanoyl, or H PO in the form of the free bases, free acids, or salts of said bases and acids, are converted by reaction with cyclic lower-alkylene and lower alkenylene esters of carbonic acid at temperatures between about 100 and.200C in good yields to compounds of the formula wherein R and R are as defined above, and R is oxygen, sulfur, imino, acetylimino, or lower-alkylimino.
The compounds of the Formula II may be hydrolyzed in a conventional manner to arabinofuranosylpyrimidine derivatives of the formula (III) 5 5 2. best yieldin terms of the pyrimidine derivative, and the term approximately equivalent, as applied to the reactants, will be understood to embrace such small excess amounts.
The reaction takes place fastest and with the best yields attemperatures between approximately and 200C, and may be performed conveniently in the presence of an inert solvent boiling in the preferred range so that thereaction temperature can be controlled by refluxing the mixture. Dimethylformamide and diacetylformamide, therefore, are suitable solvents. In some instances, the reaction is promoted by acetic anhydride or sodium carbonate as catalysts.
The compounds of Formula (II) are insoluble in many orgainc solvents, and can be precipitated from the reaction mixture by the additionof such organic solvents. They may be further purified by recrystalli zation and/or treatment with ion exchange resins or active carbon.
If it is desired to produce compounds of the Formula (Ill), it is not necessary to recover the intermediates of Formula (II), but the mixture resulting from the initial dehydration reaction may be diluted with water and made acid or alkaline to promote: the hydrolysis which leads to the arabinofuranosylpyritmidine derivatives either at room temperature (15 to 25C) or at moderately elevated temperature.
The following Examples are further illustrative of the method of the invention:
Example l A mixture of 5 g uridine and 2.5 g ethylene carbonate was heated at C for 2 hours in an oil bath. The re action mixture was cooled to room temperature and 10 ml ethanol was added. The precipitated solid was recrystallized from 15 ml methanol containing 25 percent water and then consisted of 3.3 g pure 2,2-
anhydrouridine 74% yield). It was identified by elementary analysis and had the physical properties listed below.
5 g Uridine and 2.5 g ethylene carbonate were dissolved in 10 ml N,N-dimethylformamide, and the solution was refluxed for 40 minutes. After cooling, the reaction mixture was poured into 50 ml ethanol, and the resulting crystalline precipitate was recovered by filtration. It was purified as in Example I. The needleshaped crystals so obtained consisted of pure 2,2" anhydrouridine and weighed 3 g (67 percent yield).
Example 3 A mixture of 0.42 g 5 -uridylic acid triethylamine salt and 0.6 g ethylene carbonate was heated at 150C for 90 minutes in an oil bath. The reaction mixture was passed through a column of Dowex 1 X4 (formic acid type), and the effluent was evaporated in a vacuum to obtain 0.45 g 2,2'-anhydrouridylic acid.
Formula (I) may be employed in the reaction in the free form and as the salts of suitable acids, and the phosphoric acid esters may be employed in the form of their salts with alkali metals and amines, the triethylamine, tributylamine, and morpholine salts, for example, having convenient properties.
The term lower alkyl" and analogous terms, such as lower alkanoyl," as employed in this specification and the appended claims, will be understood to cover compounds having a carbon chain of not more than four atoms.
The dehydrating agents employed in converting the compounds of Formula (1) into compounds of Formula ([1) thus include, but are not limited to, the cyclic ester of ethylene glycol with carbonic acid, hereinafter referred to as ethylene carbonate, and the corresponding propylene carbonate and vinylene carbonate. The amount of pyrimidine derivative of Formula (1) which is converted to the corresponding compound of Formula (II) is slightly less than the stoichiometric equivalent of the alkylene or alkylenyl carbonate so that it is preferred to employ a small excess of the carbonate for Example 4 A mixture of 2.8 g cytidine hydrochloride and 4.4 g ethylene carbonate was heated at 150C for 50 minutes in an oil bath. The reaction mixture was dissolved in ml water, and the solution was passed through a column packed with active charcoal. Then water was passed through the column to elute 2,2- anhydrocytidine hydrochloride. About 2 liters of the eluate were evaporated to dryness in a vacuum at 40 to 50C. The residue was recrystallized from a 1:1 mixture of water and ethanol. The columnar crystals ob tained consisted of pure 2,2'-anhydrocytidine hydrochloride and weighed 1.33 g (51 percent yield). The compound was identified by elementary analysis and had the physical properties listed below.
Example 6 2.26 g 2,2'-Anhydrouridine was dissolved in ml aqueous l N sodium hydroxide, and the solution was stirred for 2 hours at room temperature. When the absorption maximum in the ultraviolet spectrum ofa sample reached 261 u, the reaction mixture was neutralized by adding Amberlite lR-120 (H type). The ionexchange resin was filtered off, and the filtrate was evaporated to 1.7 g solid l-B-D-arabinofuranosyluracil (70.5 percent yield). The ultraviolet absorption spectrum and the melting point of the crystalline material were identical with corresponding properties of a known sample.
Example 7 2.62 g 2,2-Anhydrocytidine hydrochloride were dissolved in 80 ml aqueous 0.1 N sodium hydroxide, and the solution was allowed to stand at room temperature for 2 hours. When the absorption maximum in the ultraviolet spectrum had reached 272 u, the reaction mixture was adjusted to about pH 2 by adding I N hydrochloric acid and evaporated to dryness in a vacuum.
The residue was extracted with 100 ml hot methanol, and the extract was evaporated in a vacuum. The residue was recrystallized from a small amount of water to obtain 1.65 g 1-,B-D-arabinofuranosylcytosine hydrochloride (68 percent yield).
Example 8 0.285 g N -Acetylcytidine and 0.44 g ethylene carbonate were heated in a 10 ml flask for 2 hours in an oil bath maintained at 140C. The reaction mixture was worked up as in Example 4 to obtain 0.13 g 2,2- anhydrocytadine acetate in the form of columnar crystals.
41.28% C 4.637: H 41.38 4.83 l6.lO
240 260C (decomposed) Example 5 4.24 g 5'-Cytidylic acid triethylamine salt and 4.4 g ethylene carbonate were dissolved in 10 ml dimethylacetamide, and the solution was refluxed for 30 minutes. The reaction mixture was passed through a first column containing 200 ml Dowex l X 4 (formic acid type), and the column was washed with water. The combined effluent and washing water were passed through a second column packed with 50 ml active charcoal and eluted with water. The eluate was evaporated in a vacuum to obtain 0.4 g 2,2'-anhydrocytidine formic acid salt. The material still absorbed on the Dowex 1 X 4 in the first column was eluted with 0.2 M formic acid and the first portion of the eluate containing 2,2-anhydrocytidine- 5'-phosphoric acid was evaporated in a vacuum to obtain 0.8 g of the colorless, powdery anhydrocytidylic acid derivative.
Example 9 0.147 g N-Methylcytidine hydrochloride and 0.13 g ethylene carbonate were heated in a small flask for 30 minutes at 150C in an oil bath. Ethanol was added to the reaction mixture, and the solution was evaporated to obtain 0.11 g crystalline 2,2-anhydro-N methylcytidine hydrochloride percent yield). The UV spectrum of the compound showed values of max"'''' 6 at 243 and 267 1..
While ethylene carbonate was employed a dehydrating agent in illustrative Examples 1 to 6 and 9, the other cyclic alkylene carbonates and the alkylenyl carbonates having up to four carbon atoms in their alcohol moiety produced closely analogous or identical results when employed in equimolecular amounts.
The reaction was not significantly affected when uridine and cytidine andtheir 5-phosphoric acid esters were substituted in positions 4 and/or 5 withinthe lim with an approximately equivalent amount of a cyclic alkylene or alkylenyl ester of carbonic acid at approximately 100 to 200C until a 2,2'-anhydro derivative of said compound is formed, said anhydro derivative being of the formula in said formulas: R, being hydro xy, mercapto. amino, acetylamino, or monoalkylamino R being hydrogen, hydroxy, halogen, or alkyl,
R being hydrogen, alkanoyl, or H PO and R being oxygen, sulfur, imino, acetylimino, or alkylimino, said alkyl, alkanoyl, alkylene, and alkylenyl having not more than four carbon atoms.
2. A method as set forth in claim 1, wherein said 2.2'- anhydro derivative is recovered in substantially pure form after said forming thereof.
3. A method as set forth in claim 1, wherein said compound is reacted with said ester of carbonic acitl in the presence of dimethylformamide or diacetylformamide as a solvent substantially at the boiling temperature of said solvent.
4. A method as set forth in claim 1, wherein said carbonic acid ester is ethylene carbonate, propylene carbonate, or vinylene carbonate.
l= l =l I UNITED STATES PATENT OFFICE CERTIFiCATE O'F CORRECTEON PatentN 1 61 D d December 24- 1974 YOSHIHARU ISHIDO ET AL It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:
In the heading, line [5337, change Aj inimoto" to Ajinomoto Signed ahd sealed this 18th day of Febrfiary 1975.
(SEAL) v Attest: C. MARSHALL DANN RUTH C. MASON Commissioner of Patents Attesting Officer and Trademarks FORM po'wso HOSQ) USCQMM-DC 60376-F69 I Y 11.5. GOVERNMENT PRINTING OFFICE 9.9 0366-33l.

Claims (4)

1. A METHOD OF PRODUCING A PYRIMIDINE DERIVATIVE WHICH COMPRISES: REACTING A COMPOUND OF THE FORMULA
2. A method as set forth in claim 1, wherein said 2,2''-anhydro derivative is recovered in substantially pure form after said forming thereof.
3. A method as set forth in claim 1, wherein said compound is reacted with said ester of carbonic acid in the presence of dimethylformamide or diacetylformamide as a solvent substantially at the boiling temperature of said solvent.
4. A method as set forth in claim 1, wherein said carbonic acid ester is ethylene carbonate, propylene carbonate, or vinylene carbonate.
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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4104461A (en) * 1973-04-16 1978-08-01 Research Corporation 2,2'-Anhydro-β-D-arabinofuranosyl-5-fluorocytosine
US4267171A (en) * 1979-07-02 1981-05-12 The Regents Of The University Of California C-5 Substituted cytosine nucleosides
DE3100478A1 (en) * 1981-01-09 1982-08-12 Dr. Thilo & Co GmbH, 8021 Sauerlach 5'ESTERS OF PYRIMIDINE NUCLEOSIDES WITH ANTIVIRAL EFFECTIVENESS, METHOD FOR THE PRODUCTION AND MEDICINAL PRODUCTS THEREOF
US4418059A (en) * 1981-07-20 1983-11-29 Montefiore Medical Center Nucleoside ester compositions
US4458016A (en) * 1981-03-09 1984-07-03 Ajinomoto Co., Inc. Production of 1-β-D-ribofuranosyl-1,2,4-triazole
US5359053A (en) * 1989-08-29 1994-10-25 G. D. Searle & Co. Modified deazapyrimidines
US5399682A (en) * 1990-03-13 1995-03-21 Acic (Canada) Inc. Process for preparing 2,3'-O-cyclocytidine
WO2016110761A1 (en) * 2015-01-05 2016-07-14 Khashayar Karimian PROCESS FOR PRODUCING 1-β-D-ARABINOFURANOSYLCYTOSINE AND 2,2'-O-CYCLOCYTIDINE
CN109422788A (en) * 2017-09-05 2019-03-05 北京斯利安药业有限公司 A kind of preparation method of cytarabine hydrochloride

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS50117799A (en) * 1974-03-07 1975-09-16
JPS5927359B2 (en) * 1975-08-22 1984-07-05 田辺製薬株式会社 Production method of cytidine derivatives
JPS597719B2 (en) * 1975-10-11 1984-02-20 田辺製薬株式会社 Production method of cytidine derivatives
JPS5934720B2 (en) * 1975-11-08 1984-08-24 田辺製薬株式会社 Shichijin Yuudou Taino Seihou
EP1992632A1 (en) * 2007-05-12 2008-11-19 EXPLORA Laboratories SA Method for the synthesis of cyclouridine

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3463850A (en) * 1967-01-03 1969-08-26 Merck & Co Inc Arabinofuranosyl 2-thiopyrimidines and pharmaceutical compositions thereof
US3705147A (en) * 1969-08-22 1972-12-05 Univ Utah 3-deazapyrimidine nucleosides and method of preparation thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3463850A (en) * 1967-01-03 1969-08-26 Merck & Co Inc Arabinofuranosyl 2-thiopyrimidines and pharmaceutical compositions thereof
US3705147A (en) * 1969-08-22 1972-12-05 Univ Utah 3-deazapyrimidine nucleosides and method of preparation thereof

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4104461A (en) * 1973-04-16 1978-08-01 Research Corporation 2,2'-Anhydro-β-D-arabinofuranosyl-5-fluorocytosine
US4267171A (en) * 1979-07-02 1981-05-12 The Regents Of The University Of California C-5 Substituted cytosine nucleosides
DE3100478A1 (en) * 1981-01-09 1982-08-12 Dr. Thilo & Co GmbH, 8021 Sauerlach 5'ESTERS OF PYRIMIDINE NUCLEOSIDES WITH ANTIVIRAL EFFECTIVENESS, METHOD FOR THE PRODUCTION AND MEDICINAL PRODUCTS THEREOF
US4458016A (en) * 1981-03-09 1984-07-03 Ajinomoto Co., Inc. Production of 1-β-D-ribofuranosyl-1,2,4-triazole
US4418059A (en) * 1981-07-20 1983-11-29 Montefiore Medical Center Nucleoside ester compositions
US5359053A (en) * 1989-08-29 1994-10-25 G. D. Searle & Co. Modified deazapyrimidines
US5399682A (en) * 1990-03-13 1995-03-21 Acic (Canada) Inc. Process for preparing 2,3'-O-cyclocytidine
US5536824A (en) * 1990-03-13 1996-07-16 Acic (Canada) Inc. Organosulfonyl salts of 2,3'-O-cyclocytidine
WO2016110761A1 (en) * 2015-01-05 2016-07-14 Khashayar Karimian PROCESS FOR PRODUCING 1-β-D-ARABINOFURANOSYLCYTOSINE AND 2,2'-O-CYCLOCYTIDINE
CN109422788A (en) * 2017-09-05 2019-03-05 北京斯利安药业有限公司 A kind of preparation method of cytarabine hydrochloride
CN109422788B (en) * 2017-09-05 2020-11-20 北京斯利安药业有限公司 Preparation method of cytarabine hydrochloride

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GB1406684A (en) 1975-09-17
FR2163627B1 (en) 1976-07-02
DE2261215C2 (en) 1986-05-22
JPS5136758B2 (en) 1976-10-12
DE2261215A1 (en) 1973-06-28
JPS4867286A (en) 1973-09-13
FR2163627A1 (en) 1973-07-27

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